Peroxisomal defects in microglial cells induce a disease-associated microglial signature

Microglial cells ensure essential roles in brain homeostasis. In pathological condition, microglia adopt a common signature, called disease-associated microglial (DAM) signature, characterized by the loss of homeostatic genes and the induction of disease-associated genes. In X-linked adrenoleukodystrophy (X-ALD), the most common peroxisomal disease, microglial defect has been shown to precede myelin degradation and may actively contribute to the neurodegenerative process. We previously established BV-2 microglial cell models bearing mutations in peroxisomal genes that recapitulate some of the hallmarks of the peroxisomal β-oxidation defects such as very long-chain fatty acid (VLCFA) accumulation. In these cell lines, we used RNA-sequencing and identified large-scale reprogramming for genes involved in lipid metabolism, immune response, cell signaling, lysosome and autophagy, as well as a DAM-like signature. We highlighted cholesterol accumulation in plasma membranes and observed autophagy patterns in the cell mutants. We confirmed the upregulation or downregulation at the protein level for a few selected genes that mostly corroborated our observations and clearly demonstrated increased expression and secretion of DAM proteins in the BV-2 mutant cells. In conclusion, the peroxisomal defects in microglial cells not only impact on VLCFA metabolism but also force microglial cells to adopt a pathological phenotype likely representing a key contributor to the pathogenesis of peroxisomal disorders

Immune response of BV-2 microglial cells is impacted by peroxisomal beta-oxidation

Microglia are crucial for brain homeostasis, and dysfunction of these cells is a key driver in most neurodegenerative diseases, including peroxisomal leukodystrophies. In X-linked adrenoleukodystrophy (X-ALD), a neuroinflammatory disorder, very long-chain fatty acid (VLCFA) accumulation due to impaired degradation within peroxisomes results in microglial defects, but the underlying mechanisms remain unclear. Using CRISPR/Cas9 gene editing of key genes in peroxisomal VLCFA breakdown (Abcd1, Abcd2, and Acox1), we recently established easily accessible microglial BV-2 cell models to study the impact of dysfunctional peroxisomal β-oxidation and revealed a disease-associated microglial-like signature in these cell lines. Transcriptomic analysis suggested consequences on the immune response. To clarify how impaired lipid degradation impacts the immune function of microglia, we here used RNA-sequencing and functional assays related to the immune response to compare wild-type and mutant BV-2 cell lines under basal conditions and upon pro-inflammatory lipopolysaccharide (LPS) activation. A majority of genes encoding proinflammatory cytokines, as well as genes involved in phagocytosis, antigen presentation, and co-stimulation of T lymphocytes, were found differentially overexpressed. The transcriptomic alterations were reflected by altered phagocytic capacity, inflammasome activation, increased release of inflammatory cytokines, including TNF, and upregulated response of T lymphocytes primed by mutant BV-2 cells presenting peptides. Together, the present study shows that peroxisomal β-oxidation defects resulting in lipid alterations, including VLCFA accumulation, directly reprogram the main cellular functions of microglia. The elucidation of this link between lipid metabolism and the immune response of microglia will help to better understand the pathogenesis of peroxisomal leukodystrophies

Transcritical transient flow over mobile beds Boundary conditions treatment in a two-layer shallow-water model

River dynamic behaviour is affected by variations both in the water phase and in the transported sediment phase. A change in the water regime may lead to significant morphological changes in the bed profile, which in turn may strongly influence the flow conditions. Transcritical flows over mobile beds are particularly challenging to model due to the rapid variation in space and time of the solid transport, and to the specific treatment required for boundary conditions. The one-dimensional numerical model presented in this dissertation divides the flow in two fully coupled layers: a water layer and a water-sediment transport layer. This model was initially designed to depict dam-break flows, which does not require a specific treatment of boundary conditions. An extension of the two-layer approach is proposed in order to properly take into account boundary conditions. The treatment of boundary conditions commonly relies on characteristics. Within a two-layer model, which embodies five governing equations, an appropriate eigenstructure analysis is developed based on numerical estimations. This novel approach results in a new characterization of the critical stage by defining a specific two-layer Froude number. The model is compared to the classical Saint-Venant - Exner approach and favourably applied to several typical situations: uniform flow, which allows a straightforward calibration of the model parameters; regressive erosion around a mild-to-steep slope transition; evolution of a mobile bed under a hydraulic jump; and scour hole formation downstream of a fixed bed.(FSA 3)--UCL, 200

Soins palliatifs en onco-hématologie pédiatrique à domicile (le vécu du médecin généraliste)

RENNES1-BU Santé (352382103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

L'utilisation des venins en thérapeutique homéopathique

POITIERS-BU Médecine pharmacie (861942103) / SudocSudocFranceF

Experimental assessment of alluviation downstream of Hun-lock, Belgium

To maintain inland navigation, a deposition crest in the Hunlock area, in the Upper Meuse River, Belgium, has to be dredged almost every two years. A long-term solution is searched for, based on the understanding of water velocity field and solid transport processes, to avoid the silting and the expensive dredging. The physical process is analysed thanks to a 1:50 small-scale model of the 500 m-long Meuse reach with Hun movable dam as upstream boundary. The velocity fields, recorded with an electromagnetic probe displaced automatically, are compared for several configurations. Three discharges and distinct dam openings are tested in the existing configuration. Modifications of the downstream guard wall, by perforating ports, are also considered. Building groynes in the right side of the river is analysed. Finally, flushing water through the lock is tested. As conclusions, alluviations are due to the localisation of the lock in an enlarged area of the Upper Meuse and in a meander intrados, inducing decreasing flow velocities. None of the tested solutions is completely convincing according to 4 criterions: (1) ability to decrease the deposition crest, (2) navigation requirements, (3) safety in case of high-stage discharges, and (4) acceptable cost

Impact of the composition of polysaccharide composite gels on small molecules diffusion: A rheological and NMR study

WOS: 000274095800047 ; http://www.elsevier.com/locate/foodresInternational audienceThe gelation mechanism of carrageenan depends on the amount and nature of the polysaccharide, and is cation sensitive. From a theological approach, this specificity leads to different textural properties. In composite gels with carrageenans, starch and sucrose, the presence Of kappa/kappa 2-carrageenan, even at low levels, has an impact on textural and structural properties. In this study, theological and diffusion NMR measurements were performed on composite gels to probe gel structure at the macro- and micro-scale. Variations were made in the gel composition by varying the carrageenan content and the nature of the polysaccharide and cations. We showed that all the factors that increased the rigidity of the composite gels - polysaccharide content and specific cations - decreased significantly the diffusion of small molecules such as sucrose and ethyl butyrate. (C) 2009 Elsevier Ltd. All rights reserved

Experimental assessment of alluviation downstream of Hun-lock, Belgium

To maintain inland navigation, a deposition crest in the Hunlock area, in the Upper Meuse River, Belgium, has to be dredged almost every two years. A long-term solution is searched for, based on the understanding of water velocity field and solid transport processes, to avoid the silting and the expensive dredging. The physical process is analysed thanks to a 1:50 small-scale model of the 500 m-long Meuse reach with Hun movable dam as upstream boundary. The velocity fields, recorded with an electromagnetic probe displaced automatically, are compared for several configurations. Three discharges and distinct dam openings are tested in the existing configuration. Modifications of the downstream guard wall, by perforating ports, are also considered. Building groynes in the right side of the river is analysed. Finally, flushing water through the lock is tested. As conclusions, alluviations are due to the localisation of the lock in an enlarged area of the Upper Meuse and in a meander intrados, inducing decreasing flow velocities. None of the tested solutions is completely convincing according to 4 criterions: (1) ability to decrease the deposition crest, (2) navigation requirements, (3) safety in case of high-stage discharges, and (4) acceptable cost

Complementary approaches to understand the spreading behavior on skin of O/W emulsions containing different emollientss

International audienceThe human skin is a very complex living tissue, in a permanent evolution and self-renewing by constant lipids secretion. The characterization of this biological material is a major concern in dermo-cosmetic and pharmaceutics fields. Understanding the skin interaction with its environment, during application of skincare products, is consequently of genuine interest to better control the different phenomena occurring. In sensory language, the application of products on the skin is defined as the spreading behavior. Five O/W emulsions were formulated with different ratios of two emollients (isohexadecane and stearic acid). Complementary instrumental and sensory analysis of spreading behavior was carried out in vivo on human skin as well as in vitro on non-biological skin surface in order to investigate the impact of two emollients, and their mixtures in the spreadability and penetration of O/W emulsions. A first screening was made to link the physico-chemical properties (polarity, physical state and ratio) of emollients with the spreading behavior on human skin. Then, interesting parameters (the plateau value, its length and the increase of the friction value) from the tribological study on skin were considered to allow deepening the product/skin interactions after application of different emulsions and over time. In the last part of the study, an original method, using non-biological surfaces mimicking the human skin, was successfully tested with very good reproducibility of the spreading behavior. This original tool is of great interest to study the efficacy of new formulas on skin, but also for fundamental research and help performing standardized measurements as well as solving the logistic and safety problems of in vivo studies

Fragrance in dermocosmetic emulsions: From microstructure to skin application

Abstract Fragrance is added to almost all dermocosmetic emulsions, as it has been found to be a key driver in consumer choice and contributes to the perception of product performance. Fragrance is a complex mixture of odorant chemicals at different concentrations. When incorporated into a formulation, the individual fragrance chemicals partition between the emulsion phases depending on their physicochemical properties, which can impact the structure, stability, texture and odour of the final product. On the other hand, it is well known in the food industry how the composition and structure of food emulsion matrices influence the release of aroma chemicals. Fragranced dermocosmetic emulsions have been studied to a lesser extent but it is interesting to apply findings from the food domain since emulsion structure, composition and aroma compounds share common features. This review aims to give an overview of the literature dealing with the interactions between fragrance and dermocosmetic emulsions. The effects of fragrance on emulsion microstructure, stability and texture are highlighted and discussed. The effects of composition and structure of emulsion on the release of fragrance molecules are also presented. Finally, the interactions between skin and fragranced emulsions are addressed.Résumé Des parfums sont ajoutés dans la plupart des émulsions dermocosmétiques. L'odeur d'un produit est en effet un facteur déterminant lors du choix par les consommateurs, et elle peut même contribuer à la perception de ses performances. Le parfum est un mélange complexe de substances chimiques odorantes à différentes concentrations. Lorsqu'elles sont incorporées dans une formule, les molécules odorantes se répartissent entre les phases de l'émulsion en fonction de leurs propriétés physicochimiques, ce qui peut avoir un impact sur la structure, la stabilité, la texture et l'odeur du produit fini. D'autre part, il est bien connu dans l'industrie alimentaire que la composition et la structure des matrices alimentaires influencent la libération des molécules aromatiques. Les émulsions dermocosmétiques parfumées ont été moins étudiées dans la littérature, mais les résultats obtenus dans le domaine alimentaire peuvent être utiles pour comprendre les phénomènes mis en jeu dans ces systèmes. En effet, la structure et la composition des deux types d'émulsions, et la nature des composés aromatiques et odorants présentent de nombreuses caractéristiques communes. Cette revue vise à donner une analyse de la littérature traitant des interactions entre les parfums et les émulsions dermocosmétiques. Dans un premier temps, les effets des parfums sur la microstructure, la stabilité et la texture des émulsions sont présentés et discutés. Puis, les effets de la composition et de la structure de l'émulsion sur la libération des molécules parfumantes sont abordés. Enfin, les interactions entre la peau et les émulsions parfumées sont renseignées